In a patient with Behçet’s disease whose primary manifestation is retinal vasculitis and who is taking azathioprine 150 mg daily, should they receive both the seasonal influenza vaccine and the COVID‑19 vaccine?

Yes, this patient should receive both the seasonal influenza vaccine and the COVID-19 vaccine.

Patients with Behçet's disease presenting with retinal vasculitis who are on azathioprine 150 mg daily should receive both influenza and COVID-19 vaccines without delay or dose modification of their immunosuppressive therapy. 1

Vaccination Recommendation for This Patient

The American College of Rheumatology provides strong consensus guidance that patients with autoimmune inflammatory rheumatic diseases (AIIRDs), including Behçet's disease, should receive COVID-19 vaccination regardless of disease activity or severity (except life-threatening disease requiring ICU care) 1. This recommendation extends to influenza vaccination, which is explicitly recommended for all patients with rheumatic diseases 2.

Specific Guidance for Azathioprine

For patients taking azathioprine specifically:

• No modifications to vaccination timing are recommended 1, 3
• Do not delay or adjust vaccine administration (moderate consensus) 1
• Continue azathioprine without interruption around the time of vaccination 1

This differs markedly from medications like methotrexate (which should be held 1 week after each dose) or rituximab (which requires careful timing). Azathioprine falls into the category of immunosuppressants that may slightly reduce vaccine response but not below the threshold of seroprotection 4.

Rationale: Morbidity and Mortality Considerations

Why Vaccination is Critical in This Patient

1. Retinal vasculitis represents sight-threatening disease: Uncontrolled inflammation can lead to permanent vision loss. Any infection-related disease flare could jeopardize vision 5, 6.

2. Immunosuppression increases infection risk: Patients on azathioprine face elevated risk of severe outcomes from both influenza and COVID-19 7. The FDA label for azathioprine explicitly warns of increased susceptibility to bacterial, viral, fungal, and opportunistic infections 7.

3. Disease control takes priority: The ACR guidance emphasizes that maintaining disease stability is paramount. Interrupting azathioprine or delaying vaccination could trigger a Behçet's flare, potentially worsening retinal vasculitis 1.

4. Vaccines are safe in this population: No evidence suggests azathioprine attenuates vaccine safety, and the benefits of preventing severe respiratory infections far outweigh theoretical concerns about reduced immunogenicity 4.

Practical Implementation

Timing Strategy

• Administer both vaccines as soon as available—do not wait for "optimal" disease control if the patient is stable 1
• Influenza and COVID-19 vaccines can be co-administered on the same day 8
• Continue azathioprine 150 mg daily without interruption before, during, and after vaccination 1

Expected Vaccine Response

While azathioprine may modestly reduce antibody titers compared to immunocompetent individuals, studies show that most patients on conventional DMARDs (including azathioprine) still achieve protective immunity 4. The response is diminished but not abrogated—unlike with rituximab or high-dose methotrexate.

Monitoring Considerations

• Extended observation post-vaccination: Consider monitoring for 2 hours after vaccination due to slightly elevated risk of allergic reactions in patients with autoimmune diseases 4
• Watch for disease flare: While rare, some case reports document vasculitis flares post-vaccination 9, 10. However, the risk of infection-related flares without vaccination is substantially higher
• Do not order antibody testing: Routine serologic testing to assess vaccine response is not recommended and should not guide clinical decisions 1

Addressing the Retinal Vasculitis Concern

The presence of retinal vasculitis as the primary manifestation does not change vaccination recommendations. In fact, it strengthens the case for vaccination:

• Behçet's-related posterior uveitis and retinal vasculitis require aggressive immunosuppression (azathioprine is first-line per EULAR guidelines) 5
• Any systemic infection could trigger ocular inflammation and threaten vision
• Case reports of vaccine-associated retinal vasculitis 9, 10 are extraordinarily rare compared to the well-documented risk of infection-related disease flares in unvaccinated immunosuppressed patients

One case report describes frosted branch angiitis post-COVID vaccination in a Behçet's patient 10, but this represents a temporal association, not proven causation. The patient in that report had successful treatment with methylprednisolone and infliximab, and the authors emphasize cautious interpretation of the vaccine relationship.

Common Pitfalls to Avoid

1. Do not withhold azathioprine around vaccination time: This is unnecessary and risks disease flare 1
2. Do not delay vaccination waiting for "perfect" disease control: Unless the patient is critically ill, vaccinate promptly 1
3. Do not skip influenza vaccine focusing only on COVID-19: Both are important, and co-administration is safe 8
4. Do not order antibody titers to guide decisions: These are not validated correlates of protection in immunosuppressed patients 1

Household Contacts

Strongly encourage all household members and close contacts to receive both influenza and COVID-19 vaccines to create a "cocooning effect" that protects this immunosuppressed patient 1.